Certain 1-sulfonylbenzimidazole compounds have been found to be useful as inhibitors of viral growth (U.S. Pat. No. 4,118,742 and 4,174,454). Of this series, 2-amino-5(6)benzoyl-1-sulfonylbenzimidazoles were found to be potent antiviral agents and also to be useful as intermediates in preparing similarly active derivatives.
In the above terminology, it is recognized that an isomeric mixture of 5- and 6-benzoyl benzimidazoles is obtained when a sulfonyl chloride is allowed to react with a "tautomeric benzimidazole", i.e., a benzimidazole reactant which can be substituted at either nitrogen atom. Such an isomeric mixture of compounds is indicated by numbering the alternate positions as 5(6). Upon sulfonylation, the isomeric mixture can be resolved into the two individual compounds by means of fractional crystallization and/or by column chromatography.
Although both isomers of any given substitution were found to inhibit polio virus growth, it was recognized that the 6-isomer is generally more potent than the corresponding 5-isomer. Since the 6-isomers are preferred, and in that the separation techniques described above are expensive, time-consuming, and low yielding due to handling and the loss of half the mixture as the less desired 5-isomer, a more efficient, specific synthesis of the 6-isomer is desirable.
In supplying such a regioselective synthesis, this invention provides previously unknown compounds which are useful as intermediates in preparing 6- benzoyl-2-amino-1-sulfonylbenzimidazoles and a novel method for their preparation. Some of the novel intermediates claimed in this invention have been prepared by an alternate process as disclosed by C. W. Ryan's application filed at even date herewith entitled "Selective Sulfonation Process", Ser. No. 373,944.